Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retroviral vectors can be used as an efficient gene delivery system in a wide variety of cell types. However, in some cell types, such as embryonal carcinoma (EC) cells or normal bone-marrow cells the expression of genes introduced by retroviral vectors has been very inefficient. This expression block has severely hampered the application of retroviral vector systems in those cell types. The enhancer sequences present in the long terminal repeat (LTR) of retroviruses are known to be responsible for the tissue specificity of viral expression. Therefore, we set out to construct a vector in which this enhancer element has been replaced. A recombinant retrovirus was constructed in which the enhancer from the Moloney murine leukemia virus LTR was replaced by the enhancer of a mutant polyoma virus (PyF101) that was selected to grow on EC cells. A neomycin-resistance marker (neoR) was placed under the transcriptional control of the hybrid LTR. Following infection with this virus, neoR was expressed in EC cells, as well as in the hemopoietic progenitor cells present in normal murine bone marrow. Moreover, upon transplantation of infected bone marrow cells into lethally irradiated mice, neoR expression was sustained in hemopoietic cells of the engrafted recipients.
 ...
PMID:Retrovirus-mediated gene transfer into embryonal carcinoma and hemopoietic stem cells: expression from a hybrid long terminal repeat. 261 13

Transient expression assays were used to investigate the restriction of Moloney murine leukemia virus (MoMuLV) expression in undifferentiated mouse F9 embryonal carcinoma (EC) cells. We previously reported that the MoMuLV long terminal repeat (LTR) is inactive in undifferentiated F9EC cells due to inactivity of the tandemly repeated MoMuLV transcriptional enhancers. Others suggested that the inactivity was due to the presence of negative regulatory elements that interact with the MoMuLV tandem repeats. Two heterologous enhancer sequences that are active in undifferentiated F9 EC cells were inserted into the MoMuLV LTR: the B enhancers from the F101 variant of polyomavirus and a cellular enhancer sequence isolated from EC cells that we previously identified. The chimeric LTRs were then fused to the bacterial chloramphenicol acetyltransferase gene and tested for expression by transfection into F9 EC or NIH 3T3 cells. Insertion of these enhancers either upstream or downstream of the MoMuLV tandem repeats resulted in transcriptionally active LTRs in undifferentiated EC cells, which did not support the existence of negative regulatory elements interacting with the tandem repeats. In our previous MoMuLV enhancer deletion constructs, the GC-rich sequences downstream from the tandem repeats were also deleted, which might have contributed to the inactivity in EC cells. However, restoration of the GC-rich sequences did not yield an active LTR. The experiments also suggested that the EC cellular enhancer was preferentially active in undifferentiated EC cells and inactive in NIH 3T3 cells. The possibility of negative regulatory sequences in the vicinity of the MoMuLV primer-binding site was tested by inserting MoMuLV sequences from +30 to +419 base pairs into the LTR-chloramphenicol acetyltransferase gene constructs downstream of the transcriptional start site. Transient expression assays confirmed that these sequences reduced expression from functional LTRs in undifferentiated F9 EC cells but reduced expression significantly less in NIH 3T3 cells. Moreover, equivalent sequences from myeloproliferative sarcoma virus did not exhibit this effect. These results supported restriction of MoMuLV expression in undifferentiated F9 EC cells at two levels, inactivity of the MoMuLV enhancers and interaction of negative regulatory factors in the vicinity of the primer-binding site.
 ...
PMID:Two blocks in Moloney murine leukemia virus expression in undifferentiated F9 embryonal carcinoma cells as determined by transient expression assays. 270 78

We analyzed embryonal carcinoma cell lines infected with a recombinant Moloney murine leukemia virus. Lines that carried but did not express the neo gene retained a provirus of LTR-gag-pol-neo-LTR, where LTR is a long terminal repeat, whereas all G418-resistant lines deleted regions that included the primer binding site and the splicing donor site. This suggested the presence of multiple inhibitory elements.
 ...
PMID:Deletions in a recombinant retrovirus genome associated with its expression in embryonal carcinoma cells. 277 84

Ligand specificity of a murine gammadelta T-cell receptor-expressing hybridoma (KN6) derived from adult thymocytes has been analyzed in detail. The molecule recognized by the KN6 gammadelta T-cell receptor is expressed on syngeneic cells of various sources (peritoneal macrophages, thymocytes, spleen cells, and Abelson murine leukemia virus-transformed cell lines) and on transformed cells arrested at an early stage of development (e.g., PCC3 embryonal carcinoma cells). Linkage of the gene coding for the KN6 ligand to the major histocompatibility complex genes could be demonstrated by testing KN6 hybridoma reactivity to cells from congenic strains that differ only at H-2. In addition, analysis of recombinant strains indicates that the gene controlling the KN6 ligand is located in or distal to the TL region. Involvement of the KN6 gammadelta T-cell receptor in this recognition process could be directly demonstrated by transferring the KN6 TL specificity after introduction of the productively rearranged KN6 gamma and delta genes into an alphabeta T-cell clone or into the germ line in transgenic mice. These observations raise the possibility that at least some gammadelta cells regulate hemopoietic cell maturation and activation.
 ...
PMID:Recognition of a self major histocompatibility complex TL region product by gamma delta T-cell receptors. 278 80

Retrovirus expression is restricted in embryonal carcinoma (EC) cells but not in many differentiated cell lines. We used a very sensitive gel retardation assay to detect sequence-specific DNA-binding proteins in crude nuclear extracts obtained from EC and differentiated cells. Four binding sites were mapped in the noncoding sequences of the amphotropic murine leukemia virus. Strong binding to the CCAAT consensus sequence located in the promoter was specifically observed with EC nuclear extract. The binding protein is called EPBF (embryonal promoter-binding factor), and it is a candidate for the repressor of retrovirus transcription.
 ...
PMID:An embryonic DNA-binding protein specific for the promoter of the retrovirus long terminal repeat. 282 91

The leukomogenicity of Moloney murine leukemia virus (M-MuLV) variants with chimeric long terminal repeats (LTRs) containing sequences from polyomavirus was studied. We previously showed that insertion of the B enhancer element from the PyF101 variant into the M-MuLV LTR between the M-MuLV enhancers and promoter abolished leukemogenicity. PyF101 differs from wild-type polyoma in that it can productively infect undifferentiated F9 embryonal carcinoma cells; this is due to alterations in the B enhancer element. Two additional chimeric M-MuLVs were generated that contained the B enhancers from wild-type polyoma and also from a second host range variant (PyF441), which differs from wild-type polyoma by only a single base change. In contrast to Mo+PyF101 M-MuLV, both Mo+Pywt and Mo+-PyF441 M-MuLV induced T-lymphoid leukemia in neonatal NIH Swiss mice with the same time course as wild-type M-MuLV. Thus the lack of leukemogenicity of Mo+PyF101 M-MuLV was related to the exact nature of the PyF101 B enhancers. While both Mo+Pywt and Mo+PyF441 M-MuLVs induced leukemia, they showed differences when the resulting tumors were examined. First, approximately one-third of the tumors induced by Mo+Pywt M-MuLV contained proviruses which lacked polyoma sequences, while all of the tumors induced by Mo+PyF441 M-MuLV contained proviruses with the chimeric LTR. Second, a majority of tumors induced by Mo+Pywt M-MuLV (and also wild-type, M-MuLV) showed proviral integrations near one or more of the cellular c-myc, pim-1, or pvt-1 loci. In contrast, tumors induced by Mo+PyF441 M-MuLV showed infrequent integrations at these loci.
 ...
PMID:Leukemogenicity of Moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences. 284 57

There is a high homology of nucleotide sequence between 3' two-thirds of the X (or pX) regions of human T-cell leukemia virus (HTLV)-I, and of HTLV-II. Monoclonal antibody against p41 coded from X-IV, an open reading frame of X region of HTLV-I, was established. Two proteins coded by Xb, one of the open reading frames in X region of HTLV-II, were newly identified as p24 and p26. The expression of X protein of HTLV-II in the reconstituted mouse embryonal carcinoma cell line, which shows myoblastic morphology, reverted the morphology to that of the original embryonal carcinoma cells. This suggests that the function of X protein is to disturb the regulation of cell lineage determination. Leukemogenesis of adult T-cell leukemia (ATL) is also considered to consist of multisteps, in which HTLV-I constitutes one step, other factors also being involved. Even the role of HTLV-I factor could be similarly played by other factor(s). In agreement with this hypothesis, there are patients with ATL without associated HTLV-I.
 ...
PMID:Structure of HTLV and its biological function in leukemogenesis of adult T-cell leukemia. 288 57

From 1970 to 1985, 53 patients with malignant nondysgerminomatous germ cell tumors of the ovary underwent second-look laparotomy after initial surgery and combination chemotherapy. Twenty-two patients had immature teratoma, 15 had endodermal sinus tumor, 15 had mixed germ cell tumor, and one patient had embryonal carcinoma. Thirty-one of the neoplasms were stage I, four were stage II, 17 were stage III, and one was stage IV. Two patients received a combination of actinomycin-D, 5-fluorouracil, and cyclophosphamide; four patients received vinblastine, bleomycin, and cisplatin; 44 patients received vincristine, actinomycin-D, and cyclophosphamide; and three patients received a combination of the last two regimens. Second-look findings were negative in 52 patients and positive in one patient who was subsequently salvaged with further chemotherapy. One patient with stage I endodermal sinus tumor relapsed nine months after a negative second-look laparotomy and died. Two patients with negative findings subsequently died of leukemia. Of 53 patients undergoing second-look laparotomy, three are dead (one of cancer and two of leukemia), and 50 patients are surviving without disease. Although the precise role of second-look laparotomy in patients with malignant germ cell tumors is yet to be established, possible indications are discussed.
 ...
PMID:Second-look laparotomy in the management of malignant germ cell tumors of the ovary. 301 Feb 4

The myeloproliferative sarcoma virus (MPSV) is a unique member of the Moloney murine sarcoma virus family. Due to mutations in the U3 region of its long terminal repeat, MPSV has an expanded host range that includes cells of the hematopoietic compartment. Using a MPSV recombinant containing the gene for neomycin-resistance (NeoR-MPSV), we demonstrate that the host range of MPSV also includes undifferentiated F9 embryonal carcinoma cells. Transfer of G418-resistance with NeoR-MPSV to F9 cells is almost as efficient as G418-resistance transfer to fibroblasts, in contrast to G418-resistance transfer to PCC4 embryonal carcinoma cells, which is at least 3 orders of magnitude lower. To isolate NeoR-MPSV mutants that are efficiently expressed in PCC4 cells, G418-resistant PCC4 cell lines were induced to differentiate, and the provirus was rescued by superinfection with murine leukemia virus. Viral isolates (PCMV-5 and -6; PCMV = PCC4 cell-passaged NeoR-MPSV) were obtained and assayed for expression in embryonal carcinoma cells. The efficiency of NeoR transfer was equally as high in both F9 and PCC4 as in fibroblasts. mos oncogene expression was unaltered as judged by transformation capability. No gross alteration in the coding region and in the long terminal repeat was detectable by restriction enzyme analysis. NeoR-MPSV and its mutants PCMV-5 and -6 can thus be utilized as vectors for the efficient transduction of genes into embryonic cells.
 ...
PMID:Retroviral mutants efficiently expressed in embryonal carcinoma cells. 301 Feb 88

A derivative of the myeloproliferative sarcoma virus (Neor-MPSV) carrying the mos oncogene and dominant selection marker for neomycin resistance (Neor) was introduced into embryonal carcinoma and embryo-derived cell lines by transfection and infection using pseudotypes with Friend helper virus (Friend murine leukemia virus [F-MuLV]). Cells resistant to G418 (a neomycin analog) were cloned and expanded. Transductants retained an undifferentiated phenotype as judged by morphology, tumorigenicity, and cell-surface antigen analyses. Nucleic acid analysis of infectants revealed both Neor-MPSV and F-MuLV proviruses, although no virus was released. G418-resistant transductants remained nonpermissive for the expression of other proviruses and for subsequent superinfection. Northern analysis showed expression of full-length Neor-MPSV, as well as mos-specific subgenomic RNA. mos sequences were deleted from Neor-MPSV (Neor mos-1), and pseudotypes were used to infect embryonal carcinoma cells. No morphological differences were observed in either mos+ or mos- transductants as compared with parental cell lines. However, mos+ transductants showed an enhanced anchorage-independent growth compared with that of mos- transductants in agar cloning. PCC4 transductants were induced to differentiate with retinoic acid and superinfected with F-MuLV. Infection with viral supernatant in fibroblasts and in mice confirmed the rescue of biologically active Neor-MPSV.
 ...
PMID:Viral transfer, transcription, and rescue of a selectable myeloproliferative sarcoma virus in embryonal cell lines: expression of the mos oncogene. 302 29


<< Previous 1 2 3 4 5 6 7 8 9 Next >>